Sim Fraser J, Windrem Martha S, Goldman Steven A
Center for Translational Neuromedicine, and the Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA.
Neuron Glia Biol. 2009 Nov;5(3-4):45-55. doi: 10.1017/S1740925X09990317. Epub 2009 Oct 7.
Glial progenitor cells (GPCs) comprise the most abundant population of progenitor cells in the adult human brain. They are responsible for central nervous system (CNS) remyelination, and likely contribute to the astrogliotic response to brain injury and degeneration as well. Adult human GPCs are biased to differentiate as oligodendrocytes and elaborate new myelin, and yet they retain multilineage plasticity, and can give rise to neurons as well as astrocytes and oligodendrocytes once removed from the adult parenchymal environment. GPCs retain strong mechanisms for cell-autonomous self-renewal, and yet both their phenotype and fate may be dictated by their microenvironment. Using the transcriptional profiles of acutely isolated GPCs, we have begun to understand the operative ligand-receptor interactions involved in these processes, and have identified several key signaling pathways by which adult human GPCs may be reliably instructed to either oligodendrocytic or astrocytic fate. In addition, we have noted significant differences between the expressed genes and dominant signaling pathways of fetal and adult human GPCs, as well as between rodent and human GPCs. The latter data in particular call into question therapeutic strategies predicated solely upon data obtained using rodents, while perhaps highlighting the extent to which evolution has been attended by the phylogenetic modification of glial phenotype and function.
神经胶质祖细胞（GPCs）是成人大脑中数量最为丰富的祖细胞群体。它们负责中枢神经系统（CNS）的髓鞘再生，并且可能也参与了对脑损伤和退变的星形胶质细胞反应。成体人类GPCs倾向于分化为少突胶质细胞并形成新的髓鞘，但它们仍保留多谱系可塑性，一旦从成体实质环境中分离出来，还能产生神经元以及星形胶质细胞和少突胶质细胞。GPCs保留了强大的细胞自主自我更新机制，但其表型和命运可能都由其微环境决定。通过对急性分离的GPCs的转录谱分析，我们已开始了解这些过程中起作用的配体 - 受体相互作用，并确定了几条关键信号通路，通过这些通路可以可靠地指导成体人类GPCs走向少突胶质细胞或星形胶质细胞命运。此外，我们还注意到胎儿和成人GPCs的表达基因及主要信号通路之间，以及啮齿动物和人类GPCs之间存在显著差异。特别是后一组数据对仅基于啮齿动物数据的治疗策略提出了质疑，同时可能突出了进化在多大程度上伴随着神经胶质表型和功能的系统发育修饰。
